Resveratrol, a red wine antioxidant, reduces atrial fibrillation susceptibility in the failing heart by PI3K/AKT/eNOS signaling pathway activation

Chong, Eric; Chang, Shih Lin; Hsiao, Ya Wen; Singhal, Rahul; Liu, Shuen Hsin; Leha, Trung; Lin, Wen Yu; Hsu, Chiao Po; Chen, Yao Chang; Chen, Yi Jen; Wu, Tsu Juey; Higa, Satoshi; Chen, Shih Ann

doi:10.1016/j.hrthm.2015.01.044

Cited by 78 publications

(64 citation statements)

References 32 publications

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“…A prophylactic antibiotic agent was given as intramuscular injection for 48 hours. HF status was confirmed by the presentation of signs of ascites, edema, drowsiness, and dyspnea, which were compatible with experimental and clinical HF 4 weeks after coronary ligation 6, 7, 8…”

Section: Methodsmentioning

confidence: 68%

“…Monophasic action potentials (MAPs) were recorded during sinus rhythm from the epicardium by means of a mapping catheter at the left atrial appendage (LAA) 6, 7, 8. The MAPs were filtered from 0.05 to 500 Hz.…”

Section: Methodsmentioning

confidence: 99%

“…The action potential duration (APD) was measured from the steepest deflection of the slope of phase 0 of the MAP to the time of 90% repolarization (APD 90 ). A standardized burst pacing protocol was performed to induce AF 6. Induced AF with a minimal duration of 1 s was defined as the incidence of sustained AF 8…”

Section: Methodsmentioning

confidence: 99%

“…The patients with MI who developed AF are at a greater risk for HF‐related hospitalization and mortality than those without AF 3, 5. In an ischemic HF rabbit model, structural and electrical remodeling in the atrium were observed, which was associated with high AF inducibility 6, 7, 8. The activity of the phosphoinositide 3‐kinase (PI3K)/AKT/endothelial nitric oxide synthase (eNOS) signaling pathway plays an important role in the inhibition of pathologic signaling cascades in AF 6…”

Section: Introductionmentioning

confidence: 99%

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Impact of Renal Denervation on Atrial Arrhythmogenic Substrate in Ischemic Model of Heart Failure

Yamada

Fong

Hsiao

et al. 2018

JAHA

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BackgroundMyocardial infarction increases the risk of heart failure (HF) and atrial fibrillation. Renal denervation (RDN) might suppress the development of atrial remodeling. This study aimed to elucidate the molecular mechanism of RDN in the suppression of atrial fibrillation in a HF model after myocardial infarction.Methods and Results HF rabbits were created 4 weeks after coronary ligation. Rabbits were classified into 3 groups: normal control (n=10), HF (n=10), and HF‐RDN (n=6). Surgical and chemical RDN were approached through midabdominal incisions in HF‐RDN. Left anterior descending coronary artery in HF and HF‐RDN was ligated to create myocardial infarction. After electrophysiological study, the rabbits were euthanized and the left atrial appendage was harvested for real‐time polymerase chain reaction analysis and Trichrome stain. Left atrial dimension and left ventricular mass were smaller in HF‐RDN by echocardiography compared with HF. Attenuated atrial fibrosis and tyrosine hydroxylase levels were observed in HF‐RDN compared with HF. The mRNA expressions of Cav1.2, Nav1.5, Kir2.1, KvLQT1, phosphoinositide 3‐kinase, AKT, and endothelial nitric oxide synthase in HF‐RDN were significantly higher compared with HF. The effective refractory period and action potential duration of HF‐RDN were significantly shorter compared with HF. Decreased atrial fibrillation inducibility was noted in HF‐RDN compared with HF (50% versus 100%, P<0.05).Conclusions RDN reversed atrial electrical and structural remodeling, and suppressed the atrial fibrillation inducibility in an ischemic HF model. The beneficial effect of RDN may be related to prevention of the downregulation of the phosphoinositide 3‐kinase/AKT/endothelial nitric oxide synthase signaling pathway.

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Section: Methodsmentioning

confidence: 68%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Impact of Renal Denervation on Atrial Arrhythmogenic Substrate in Ischemic Model of Heart Failure

Yamada

Fong

Hsiao

et al. 2018

JAHA

Self Cite

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show abstract

“…In the present study, resveratrol treatment significantly increased the expression of eNOS expression in rats with STZ-DRMI. Chong et al (30) previously reported that resveratrol was able to reduce susceptibility to atrial fibrillation via activating the PI3K/AKT/eNOS signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Protective effects of resveratrol improve cardiovascular function in rats with diabetes

Yan

Sun

2017

Exp Ther Med

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Abstract.Resveratrol is a flavonoid with a stilbene structure that is able to suppress acute pulmonary thromboembolism-induced pulmonary artery hypertension. Furthermore, it possesses anti-cancer and antioxidant properties, is able to regulate blood lipids and increase life expectancy. In the present study, it was evaluated whether the protective effect of resveratrol was able to improve cardiovascular function in rats with diabetes. The effects of resveratrol on blood glucose, body weight, heart/body weight ratio, plasma triglyceride levels, heart rate, aspartate transaminase (AST)/alanine transaminase (ALT) ratio and total plasma insulin were evaluated. Levels of inflammation and oxidative stress were also evaluated using ELISA kits, and the expressions of endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF) and phosphorylated (p)-p38 protein were evaluated via western blot analysis. The results demonstrated that administration of resveratrol in rats with diabetes-related myocardial infarction (DRMI) significantly reduced blood glucose, body weight, plasma triglyceride levels, heart rate and AST/ALT ratio (all P<0.01) and significantly increased total plasma insulin (P<0.01). Furthermore, resveratrol significantly reduced levels of inflammation factors (P<0.01) and malondialdehyde, a marker for oxidative stress, in rats with DRMI (P<0.01). Resveratrol significantly increased the expression of eNOS (P<0.01) and suppressed the expression of VEGF and p-p38 (both P<0.01) in rats with DRMI. These results suggest that treatment with resveratrol is able to improve cardiovascular function via inhibition of eNOS and VEGF, and suppression of p38 phosphorylation in rats with DRMI.

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Neuro‐Protective Effects of Resveratrol on Carbon Monoxide‐Induced Toxicity in Male Rats

Tabrizian

Shahraki

Bazzi

et al. 2017

Phytotherapy Research

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Acute carbon monoxide (CO) poisoning causes neurotoxicity through induction of necrosis, apoptosis, lipid peroxidation and oxidative stress. Resveratrol (RES) is a natural polyphenolic phytoalexin that exhibits neuroprotective effects in ischemia/reperfusion due to its anti-apoptotic, anti-necrotic and strong anti-oxidant properties as well as its ability to activate pro-survival pathways. In this study, rats were exposed to CO 3000 ppm for 1 h. Immediately after poisoning and on the next four consecutive days, RES (1, 5 and 10 mg/kg) was administered intraperitoneally. On the fifth day, animals' brains were excised, and necrosis, lipid peroxidation level and the level of Akt, BAX and BCL2 expression were evaluated. The results showed that RES 10 mg/kg significantly reduced lipid peroxidation, but RES 1 and 5 mg/kg had no significant effect on this parameter. Furthermore, RES 5 and 10 mg/kg significantly increased Akt expression level, while BAX/BCL2 ratio was reduced by RES 1, 5 and 10 mg/kg. Moreover, RES reduced necrotic foci in the brain, but the best results were seen following treatment with RES 10 mg/kg. In summary, RES showed neuroprotective effect in CO-poisoned rats as it decreased necrosis and BAX/BCL2 ratio and increased Akt expression levels. Copyright © 2017 John Wiley & Sons, Ltd.

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Resveratrol, a red wine antioxidant, reduces atrial fibrillation susceptibility in the failing heart by PI3K/AKT/eNOS signaling pathway activation

Cited by 78 publications

References 32 publications

Impact of Renal Denervation on Atrial Arrhythmogenic Substrate in Ischemic Model of Heart Failure

Impact of Renal Denervation on Atrial Arrhythmogenic Substrate in Ischemic Model of Heart Failure

Protective effects of resveratrol improve cardiovascular function in rats with diabetes

Neuro‐Protective Effects of Resveratrol on Carbon Monoxide‐Induced Toxicity in Male Rats

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